Attention Deficit/Hyperactivity DisorderPhase 3NCT01259492
Efficacy and Safety Study of Methylphenidate Hydrochloride Extended Release in Adults With Childhood-onset Attention Deficit/Hyperactivity Disorder (ADHD)
A Phase 3 study testing Ritalin LA 20 mg and Ritalin LA 30 mg in people with Attention Deficit/Hyperactivity Disorder, run by Novartis Pharmaceuticals at 68 sites in 9 countries.
Trial summary
This study will evaluate efficacy and safety of methylphenidate hydrochloride extended release compared to placebo in adult patients with childhood-onset attention deficit/hyperactivity disorder (ADHD). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Attention Deficit/Hyperactivity Disorder
- What is being tested?
- Ritalin LA 20 mg and Ritalin LA 30 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 725 participants
- Where
- 68 sitesin 9 countries
- Study dates
- Nov 2010to Aug 2012
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosis of attention deficit/hyperactivity disorder (ADHD) which started in childhood
- Female patients of childbearing potential must be practicing an acceptable method of contraception.
Who cannot join
- Patients with body mass index (BMI) less than 18.5 kg/m2 or more than 35 kg/m2
- History of alcohol or substance abuse within the last six months.
- History of seizures or use of anticonvulsant medication.
- Any psychiatric condition that requires medication or may interfere with study participation.
- Pre-existing cardiovascular disorders including severe hypertension, heart failure, myocardial infraction, etc.
- Significant respiratory, hepatic, gastrointestinal, renal, hematological or oncologic disorder
Show all 10Show fewer
- Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma
- Diagnosis or family history of Tourette's syndrome
- Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
68 sites in 9 countries.
68 sites in 9 countries
Germany28 sites
Novartis Investigative Site
Ahrensburg, Germany, 22926
Novartis Investigative Site
Bamberg, Germany, 96047
Novartis Investigative Site
Berlin, Germany, 12200
Novartis Investigative Site
Berlin, 10629
Novartis Investigative Site
Dresden, 01129
Novartis Investigative Site
Ellwangen, 73479
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Freiburg im Breisgau, 79104
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Hagen, 58093
Novartis Investigative Site
Hamburg, Germany, 20259
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Homburg, 66421
Novartis Investigative Site
Kiel, Germany, 24105
Novartis Investigative Site
Landau, 76829
Novartis Investigative Site
Leipzig, 04157
Novartis Investigative Site
Limburg, 65549
Novartis Investigative Site
Ludwigsburg, Germany, 71636
Novartis Investigative Site
Mainz, Germany, 55131
Novartis Investigative Site
Mannheim, 68159
Novartis Investigative Site
München, Germany, 80333
Novartis Investigative Site
Naumburg, Germany, 06618
Novartis Investigative Site
Nuremberg, Germany, 90419
Novartis Investigative Site
Siegen, 57076
Novartis Investigative Site
Ulm, 89081
Novartis Investigative Site
Westerstede/Oldenburg, 26655
Novartis Investigative Site
Wolfsburg, Germany, 38444
Novartis Investigative Site
Würzburg, 97070
United States21 sites
Novartis Investigative Site
Bellevue, Washington, 98004
Novartis Investigative Site
Beverly Hills, California, 90210
Novartis Investigative Site
Bradenton, Florida, 34208
Novartis Investigative Site
Columbus, Ohio, 43210
Novartis Investigative Site
Fargo, North Dakota, 58103
Novartis Investigative Site
Houston, Texas, 77007
Novartis Investigative Site
Houston, Texas, 77008
Novartis Investigative Site
Las Vegas, Nevada, 89119
Novartis Investigative Site
Las Vegas, Nevada, 89128
Novartis Investigative Site
Libertyville, Illinois, 60048
Novartis Investigative Site
Little Rock, Arkansas, 72205
Novartis Investigative Site
Miami, Florida, 33173
Novartis Investigative Site
Oklahoma City, Oklahoma, 73112
Novartis Investigative Site
Orlando, Florida, 32806
Novartis Investigative Site
Owensboro, Kentucky, 42301
Novartis Investigative Site
Philadelphia, Pennsylvania, 19149
Novartis Investigative Site
Seattle, Washington, 98104
Novartis Investigative Site
Spring Valley, California, 91978-1522
Novartis Investigative Site
Troy, Michigan, 48083
Novartis Investigative Site
West Plam Beach, Florida, 33407
Novartis Investigative Site
Willingboro, New Jersey, 08046
Belgium6 sites
Novartis Investigative Site
Bruges, Belgium, 8310
Novartis Investigative Site
Heusden-Zolder, Belgium, 3550
Novartis Investigative Site
Kessel-Lo, 3010
Novartis Investigative Site
Kortenberg, Belgium, 3070
Novartis Investigative Site
Mechelen, 2800
Novartis Investigative Site
Uccle, Belgium, 1180
Colombia3 sites
Novartis Investigative Site
Antioquia
Novartis Investigative Site
Bogotá
Novartis Investigative Site
Santa Fe de Antioquia, Antioquia, 0000
South Africa3 sites
Novartis Investigative Site
Benoni
Novartis Investigative Site
Melrose Arch, 2196
Novartis Investigative Site
Pretoria, 0001
Sweden3 sites
Novartis Investigative Site
Luleå, 972 35
Novartis Investigative Site
Malmö, 211 53
Novartis Investigative Site
Stockholm, 141 86
Norway2 sites
Novartis Investigative Site
Porsgrunn, Norway, 3922
Novartis Investigative Site
Skien, 3725
About this study
Official title: A 40-week, Randomized, Double-blind, Placebo-controlled, Multicenter Efficacy and Safety Study of Methylphenidate HCl Extended Release in the Treatment of Adult Patients With Childhood-onset ADHD
This study will evaluate efficacy and safety of methylphenidate hydrochloride extended release compared to placebo in adult patients with childhood-onset attention deficit/hyperactivity disorder (ADHD).
- Conditions
- Attention Deficit/Hyperactivity Disorder
- Being tested
- Placebo, Ritalin LA 20 mg, Ritalin LA 30 mg
- Keywords
- Attention Deficit /Hyperactivity Disorder, hyperactivity
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo Comparator: Placebo
Ritalin LA 20 mgDrug
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 40, 60, or 80 mg.
Ritalin LA 30 mgDrug
Ritalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 60, or 80 mg.
| Study group | Role | What they receive |
|---|---|---|
| Ritalin LA 40 mg | Experimental | In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2, continued in same dose till week 9. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 40 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14. In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. Receives: Drug: Ritalin LA 20 mg |
| Ritalin LA 60 mg | Experimental | In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2 and to 60 mg at week 3. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 60 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14.In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. Receives: Drug: Ritalin LA 20 mg; Drug: Ritalin LA 30 mg |
| Ritalin LA 80 mg | Experimental | In period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2 and to 60 mg at week 3 and to 80 mg at week 4. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 60 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14. In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. Receives: Drug: Ritalin LA 20 mg; Drug: Ritalin LA 30 mg |
| Placebo | Placebo comparator | Period 1- Placebo controlled Period 2 - The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose (40, 60 or 80 mg). In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment
Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) total score consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The DSM-IV ADHD RS total score was calculated as the sum of the Inattentive and the Hyperactive-Impulsive subscores. The 18 items are rated from 0 ("Never") to 4 ("Very often"). The total score ranges from 0(least symptomatic) to 72 (most symptomatic). Decrease in the DSM-IV ADHD RS total score indicates improvement, therefore a greater decrease (change at Final Visit compared to baseline) indicates a greater improvement in ADHD symptoms. 30% improvement: 100×(DSM-IV ADHD RS total score during Period 1 - DSM-IV ADHD RS total score at randomization(visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) <= - 30%.
Measured: Baseline 1 to End of Period 1 (Week 9)
Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment
SDS, a 5-self-rated questionnaire to measure the extent a pt's disability due to an illness/health problem interferes with work/school, social life/leisure, family life/home. First 3 items, pts are asked how their symptoms disrupted their reg. activities over the past 7d in ea. using a scale from 0(not at all)-10(extremely) Ea. subscale(work disability, social life disability, family life disability) can be scored independently or combined into a total score(sum of the non-missing responses for items 1-3)from 0-30,higher scores indicate significant functional impairmt. Subscale scores >5 suggest impairment in that subscale area. Final 2 items ask pts about the # of days their symptoms caused them to miss school/work and # of days their symptoms caused them to be underproductive at school/work.(These items were not included in the total score.) Before responding to SDS items 1-3, pts were verbally instructed to recall the past 7d, items 4-5 refer to the last week w/in the item wording.
Measured: Baseline 1 to End of Period 1 (Week 9)
Percentage of Participants With Treatment Failures During Period 3
Treatment failure is defined as: 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at re-randomization (visit 13))/DSM-IV ADHD RS total score at re-randomization (visit 13) >= 30% AND 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at randomization (visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) > - 30%. The ADHD-RS-IV is an 180item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54
Measured: Baseline Period 1 (Baseline 1) and Baseline Period 3 (Baseline 2) to End of Week 40
Secondary outcomes (10)
Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1
On the CGI-I scale, a lower score reflects greater improvement between 1 and 3, a score of 4 is "no change", scores higher than 4 reflect worsening. The CGI-I consists of 7 ratings that range from 1 = "Very much improved" to 7 ="Very much worse". Improvement on the CGI-I scale is defined as a visit rating of 1 "very much improved" or 2 "much improved" on the CGI-I scale. Percentage has been calculated from the evaluable patients (N) as Percentage = n/N * 100.
Measured: Baseline 1 to End of Period 1 (Week 9)
Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14)
DSM-IV ADHD RS consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The SDS is a five-item, self-rated questionnaire that has been used widely in clinical trials and observational studies. CAARS-O: S consists of 26 items and 6 subscales: Inattention/Memory Problems, Hyperactivity/Restlessness, Impulsivity/Emotional Lability, Problems with Self-Concept, ADHD Index, and Inconsistency Index and is rated by someone close to the patient in their daily life such as a spouse, friend, or coworker. The Adult Self-Report Scale (ASRS) is a self-rating scale designed to assess Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. The 18 items are written to reflect the DSM-IV diagnostic criteria for ADHD and are rated from 0 ("Never") to 4 ("Very often").
Measured: Baseline 1 to End of Period 2 (Week 14)
Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14)
CGI-I assesses the overall change of illness relative to baseline. CGI-I consists of 7 ratings that range from 1 = "very much improved", 2 = "much improved", 3 = "minimally improved", 4 = "no change from baseline", 5 = "minimally worse", 6 = "much worse" 7 = "very much worse"
Measured: Baseline 1 to End of Period 2 (Week 14)
Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14)
CGI-S assesses the patient's current illness state. CGI-S consists of 7 ratings that range from 1 = "normal, not at all ill" , 2 = "borderline mentally ill", 3 =" mildly ill", 4 = "moderately ill", 5 = "markedly ill", 6 = "severely ill", 7 = "among the most extremely ill patients"
Measured: Baseline 1 to End of Period 2 (Week 14)
Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment
The ADHD-RS-IV is an 180 item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54.
Measured: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment
The Sheehan Disability Scale (SDS) is a self-rating scale designed to assess the extent to which the patient's work social life/leisure activities and home life are impaired by his or her symptoms. The scale generates 4 scores: a work disability score, a social life disability score, a family life disability score and a total score. To get a total score the 3 individual scores (work: social life: family life) are totaled. The maximum possible score is 30 The higher the score, the more "impaired" a patient's work, social life, family life is.
Measured: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment
On the CGI-I scale, a lower score reflects greater improvement between 1 and 3, a score of 4 is "no change", scores higher than 4 reflect worsening. The CGI-I consists of 7 ratings that range from 1 = "Very much improved" to 7 ="Very much worse". Improvement on the CGI-I scale is defined as a visit rating of 1 "very much improved" or 2 "much improved" on the CGI-I scale.
Measured: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment
CGI-S assesses the patient's current illness state. CGI-S consists of 7 ratings that range from 1 = "normal, not at all ill" , 2 = "borderline mentally ill", 3 =" mildly ill", 4 = "moderately ill", 5 = "markedly ill", 6 = "severely ill", 7 = "among the most extremely ill patients"
Measured: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment
CAARS is an instrument to assess ADHD symptoms and behaviors in adults. This study utilizes the Observer Short Version (CAARS-O: S), consisting of 26 items and 6 subscales: Inattention/Memory Problems, Hyperactivity/Restlessness, Impulsivity/Emotional Lability, Problems with Self-Concept, ADHD Index (to distinguish ADHD adults from non-clinical adults), and Inconsistency Index (to identify random or careless responding) and is rated by someone close to the patient in their daily life such as a spouse, friend, or coworker. The observer is asked to notice the patient carefully and decide how much or how frequently each of the 26 items of the scale describes the patient recently. The response to every question in increasing order of severity is "not at all, never = 0; Just a little, once in a while = 1; Pretty much, often = 2; Very much, very frequently = 3". The total score combined from all the 26 items ranges from 0 to 88.
Measured: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment
The ASRS is a self-rating scale designed to assess ADHD symptoms in adults and is now part of the World Health Organization Composite International Diagnostic Interview. It consists of 18 items written to reflect the DSM-IV diagnostic criteria for ADHD and are rated from 0 ("Never") to 4 ("Very often"). The total score ranges from 0 to 72.
Measured: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2010 (estimated)
- Study startNov 2010
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit/Hyperactivity DisorderStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 725 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01259492
- Sponsor's protocol ID
- CRIT124D2302
- Other IDs
- 2010-021533-31
- Status last verified
- Sep 2014
- First submitted
- 11 Dec 2010
- Last updated
- 7 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Huss M, Ginsberg Y, Tvedten T, Arngrim T, Philipsen A, Carter K, Chen CW, Kumar V. Methylphenidate hydrochloride modified-release in adults with attention deficit hyperactivity disorder: a randomized double-blind placebo-controlled trial. Adv Ther. 2014 Jan;31(1):44-65. doi: 10.1007/s12325-013-0085-5. Epub 2013 Dec 27.
PubMed 24371021
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 40-week, Randomized, Double-blind, Placebo-controlled, Multicenter Efficacy and Safety Study of Methylphenidate HCl Extended Release in the Treatment of Adult Patients With Childhood-onset ADHD
- ClinicalTrials.gov ID
- NCT01259492
- Acronym / sponsor ID
- CRIT124D2302
- Conditions
- Attention Deficit/Hyperactivity Disorder
- Keywords
- Attention Deficit /Hyperactivity Disorder, hyperactivity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 725 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2010
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 14 Dec 2010 (estimated)
- Results
- Posted 29 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate efficacy and safety of methylphenidate hydrochloride extended release compared to placebo in adult patients with childhood-onset attention deficit/hyperactivity disorder (ADHD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Ritalin LA 40 mg | Experimental | Drug: Ritalin LA 20 mgIn period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2, continued in same dose till week 9. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 40 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14. In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. |
| Ritalin LA 60 mg | Experimental | Drug: Ritalin LA 20 mg, Drug: Ritalin LA 30 mgIn period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2 and to 60 mg at week 3. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 60 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14.In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. |
| Ritalin LA 80 mg | Experimental | Drug: Ritalin LA 20 mg, Drug: Ritalin LA 30 mgIn period 1 patients were given Ritalin LA 20 mg and up titrated to 40 mg at week 2 and to 60 mg at week 3 and to 80 mg at week 4. Period 2- The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose 60 mg. Optimal dose was defined as the dose at which the investigator considered an optimal balance between control of symptoms and side effects was maintained for a period of at least one week prior to Week 14. In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. |
| Placebo | Placebo comparator | Drug: PlaceboPeriod 1- Placebo controlled Period 2 - The dose of study medication was re-titrated for all patients (including those in the Placebo arm during Period 1) starting at 20 mg/day Ritalin LA and increased at weekly intervals in increments of 20 mg/day until reaching the patient's optimal dose (40, 60 or 80 mg). In period 3, patients were re- randomized to either their optimal dose of medication (40, 60, or 80 mg/day) or Placebo from beginning of week 15 to end of week 40. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Diagnosis of attention deficit/hyperactivity disorder (ADHD) which started in childhood
- Female patients of childbearing potential must be practicing an acceptable method of contraception.
Key exclusion criteria (10 listed)
- Patients with body mass index (BMI) less than 18.5 kg/m2 or more than 35 kg/m2
- History of alcohol or substance abuse within the last six months.
- History of seizures or use of anticonvulsant medication.
- Any psychiatric condition that requires medication or may interfere with study participation.
- Pre-existing cardiovascular disorders including severe hypertension, heart failure, myocardial infraction, etc.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboPlacebo Comparator: Placebo | Drug | Placebo |
| Ritalin LA 20 mgRitalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 40, 60, or 80 mg. | Drug | Ritalin LA 40 mg, Ritalin LA 60 mg, Ritalin LA 80 mg |
| Ritalin LA 30 mgRitalin LA (a racemic mixture of d- and l-thre-Methylphenidate Hydrochloride (MPH), extended release hard capsules) taken orally once daily in doses of 60, or 80 mg. | Drug | Ritalin LA 60 mg, Ritalin LA 80 mg |
Primary outcome
Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment
Time frame: Baseline 1 to End of Period 1 (Week 9)
Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) total score consists of 18 items directly adapted from the ADHD symptom list according to the DSM-IV. The DSM-IV ADHD RS total score was calculated as the sum of the Inattentive and the Hyperactive-Impulsive subscores. The 18 items are rated from 0 ("Never") to 4 ("Very often"). The total score ranges from 0(least symptomatic) to 72 (most symptomatic). Decrease in the DSM-IV ADHD RS total score indicates improvement, therefore a greater decrease (change at Final Visit compared to baseline) indicates a greater improvement in ADHD symptoms. 30% improvement: 100×(DSM-IV ADHD RS total score during Period 1 - DSM-IV ADHD RS total score at randomization(visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) <= - 30%.
Change From Baseline Period 1 (Baseline 1) to End of Period 1 on Sheehan Disability Scale (SDS) Total Score by Treatment
Time frame: Baseline 1 to End of Period 1 (Week 9)
SDS, a 5-self-rated questionnaire to measure the extent a pt's disability due to an illness/health problem interferes with work/school, social life/leisure, family life/home. First 3 items, pts are asked how their symptoms disrupted their reg. activities over the past 7d in ea. using a scale from 0(not at all)-10(extremely) Ea. subscale(work disability, social life disability, family life disability) can be scored independently or combined into a total score(sum of the non-missing responses for items 1-3)from 0-30,higher scores indicate significant functional impairmt. Subscale scores >5 suggest impairment in that subscale area. Final 2 items ask pts about the # of days their symptoms caused them to miss school/work and # of days their symptoms caused them to be underproductive at school/work.(These items were not included in the total score.) Before responding to SDS items 1-3, pts were verbally instructed to recall the past 7d, items 4-5 refer to the last week w/in the item wording.
Percentage of Participants With Treatment Failures During Period 3
Time frame: Baseline Period 1 (Baseline 1) and Baseline Period 3 (Baseline 2) to End of Week 40
Treatment failure is defined as: 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at re-randomization (visit 13))/DSM-IV ADHD RS total score at re-randomization (visit 13) >= 30% AND 100×(DSM-IV ADHD RS total score during Period 3 - DSM-IV ADHD RS total score at randomization (visit 2))/DSM-IV ADHD RS total score at randomization (visit 2) > - 30%. The ADHD-RS-IV is an 180item clinician rated scale to assess ADHD by DSM-IV-TR, defined criteria using symptom terminology appropriate for the adult population. Each item pertains to inattention (odd-numbered) or hyperactivity/impulsivity (even-numbered) and is scored on a scale of 0 (no symptoms) to 3 (severe symptoms). A total added score can range from 0-54
10 secondary outcomes
Percentage of Patients With Improvement on Clinical Global Impression - Improvement Scale (CGI-I) From Baseline Period 1 (Baseline 1) to End of Period 1
Time frame: Baseline 1 to End of Period 1 (Week 9)
Change From Baseline 1 in DSM-IVADHD RS Total Score, SDS Total Score, The Conners' Adult ADHD Rating Scale Observer Short Version (CAARS-O:S) Total Score and Adult Self-Report Scale (ASRS) Total Score at the End of Period 2 (Visit 13/ Week 14)
Time frame: Baseline 1 to End of Period 2 (Week 14)
Number of Participants With Clinical Global Impression - Improvement Scale (CGI-I) Rating at the End of Period 2 (Visit 13/ Week 14)
Time frame: Baseline 1 to End of Period 2 (Week 14)
Number of Participants With Clinical Global Impression - Improvement Scale Severity of Illness (CGI-S) Rating at the End of Period 2 (Visit 13/ Week 14)
Time frame: Baseline 1 to End of Period 2 (Week 14)
Change From Baseline Period 3 (Baseline 2) to End of Period 3 on DSM-IV Attention-Deficit/Hyperactivity Disorder Rating Scale ADHD RS Total Score by Treatment
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Change From Baseline Period 3 (Baseline 2) to End of Period 3 on SDS Total Score by Treatment
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Number of Patients With Worsening on CGI-I Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Number of Patients With Worsening on CGI-S Scale From Baseline Period 3 (Baseline 2) to End of Period 3 by Treatment
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Change From Baseline Period 3 (Baseline 2) to End of Period 3 in Conners Adult ADHD Rating Scales Observer: Short Version (CAARS-O:S:) Total Score by Treatment
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Change From Baseline Period 3 (Baseline 2) to End of Period 3 in ASRS Total Score by Treatment
Time frame: Baseline 2 to end of Period 3 (end of withdrawal period 40 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24371021Huss M, Ginsberg Y, Tvedten T, Arngrim T, Philipsen A, Carter K, Chen CW, Kumar V. Methylphenidate hydrochloride modified-release in adults with attention deficit hyperactivity disorder: a randomized double-blind placebo-controlled trial. Adv Ther. 2014 Jan;31(1):44-65. doi: 10.1007/s12325-013-0085-5. Epub 2013 Dec 27.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
68 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ritalin LA 20 mg and Ritalin LA 30 mg in people with Attention Deficit/Hyperactivity Disorder, run by Novartis Pharmaceuticals at 68 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in Germany, United States, Belgium, Colombia, South Africa and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline of Period 1 (Baseline 1) to End of Period 1 on Attention-Deficit/Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) Total Score by Treatment (time frame: Baseline 1 to End of Period 1 (Week 9)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01259492, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2014.